Every drug has the potential to cause side effects. With aminoglycosides, a group of antibiotics that includes those used to treat tuberculosis and other serious infections, hearing loss can affect as many as 20% of people taking the drug. Despite a spate of efforts, there is currently no treatment or prevention for the damage to sensory cells caused by these drugs.
However, in a paper published today, in the Journal of Clinical Investigation, Lisa Cunningham and her colleagues at the US National Institute on Deafness and Other Communication Disorders in Bethesda, Maryland, show that the protective effect of a heat shock protein, HSP70, may provide a new therapeutic option to prevent inner ear cells injury by these antibiotics.
Heat shock proteins (HSPs) are produced by cells in response to stress, such as a sudden spike in temperature. Dubbed ‘molecular chaperones’, HSPs may be best known for their stabilizing role inside cells where they help sort, separate and fold other proteins. But scientists continue to discover the protective role that heat shock proteins can play outside of cells—from activating the body’s defense system to helping repair injured muscle. With a lengthening research record of showing up when cells get injured, HSP70 may be a good therapeutic focus to avert aminoglycoside-induced hair cell death.
“We know diseases can be caused where there is deficient or inadequate chaperone function,” says Rona Giffard, a neuroscientist at Stanford Medical School, in Palo Alto, California. If researchers find a way to increase HSP70 in areas where cells could be harmed, that ability to create a ‘super-response’ may give us ways to support cells that are stressed and unlikely to survive, Giffard says. “We might be able to push cells over the edge, to survival.”
From previous mouse studies, Cunningham knew that inner ear cells exposed to high temperatures released HSP70 and, under those circumstances, the hair cells in the ear that are critical to hearing were spared from antibiotic damage. Her team had also shown that HSP70 was necessary for that protection to occur.
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In the new study, she again used cell cultures derived from mouse utricles, an organ with hair cells similar to the inner ear cells of people, to explore the mechanism behind HSP70’s protective effect. Her team found that the cells that surrounded and supported the antibiotic-sensitive hair cells—rather than the hair cells themselves— were responsible for releasing HSP70, and conferring protection. But more importantly, when the research team used utricle cultures that couldn’t generate their own HSP70–and didn’t heat shock them–but then added both an aminoglycoside and human HSP70 to those cultures, the hair cells remained unscathed.
Although it still isn’t clear how the hair cells are saved by HSP70, these tests show the presence of the protein outside the hair cells is enough to induce protection, says Cunningham. Moreover, by releasing HSP70 in response to stress, the supporting cells have a critical role in determining whether the hair cells live or die.
Further studies are needed to understand how the hair cells signal for help, and then how HSP70 manages the rescue response. However, Cunningham and her colleagues are also working on the design of a clinical trial to see if pushing HSP70 production in human ears can prevent hearing loss before drugs do their damage.
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